Nurture over nature in new Micromonospora spp. strains’ metabolism: multi-omics analyses reveal fermentation conditions as the dominant driver over phylogeny

The genus Micromonospora , a key member of the actinomycetes, has demonstrated considerable potential for natural product biosynthesis. In this study, we isolated 15 Micromonospora spp. strains from desert soil and marine sediment samples, eight of which represent four novel species. To explore the biosynthetic capacity of this genus, we performed an integrated analysis of Micromonospora reference genomes. Pan-genomic analysis further unveiled the core biosynthetic characteristics of the genus responsible for producing terpenes and polyketides. Further multi-omics investigation, combining genomic and metabolomic data, uncovered a positive correlation between phylogenetic relationships and biosynthetic potential, alongside a decoupling of metabolic profiles. Notably, metabolomic findings emphasized the dominant influence of culture conditions on the expression of biosynthetic capabilities. Overall, our study provides a comprehensive elucidation of the biosynthetic potential of the genus Micromonospora and highlights the value of investigating novel strains and applying diverse cultivation strategies in natural product discovery.